Phenylalanine is a very important amino acid that is a precursor to key neurotransmitters. It can help reduce pain and treat vitiligo. In addition, it has an energizing and cognitive-enhancing effect by increasing dopamine and other catecholamine levels. Continue reading to learn about the health benefits and side effects of phenylalanine supplementation.

What is Phenylalanine?

Phenylalanine (or L-phenylalanine, or DL-phenylalanine) is a nonpolar, neutral amino acid. It is also essential for different bodily processes and must be obtained from the diet as it cannot be synthesized endogenously.

Phenylalanine is required for the production of tyrosine (another amino acid), and neurotransmitters such as dopamine, norepinephrine, and epinephrine [R].

Phenylalanine can be found in many protein-rich foods such as eggs, dairy, chicken, and beef.

Different Forms of Phenylalanine Supplements

There are three main types of phenylalanine supplements: D, L, and DL-phenylalanine.

  • L-phenylalanine is the natural version of the supplement and is found in the proteins of the body and in foods.
  • D-phenylalanine is a mirror image of L-phenylalanine, but it is synthesized in the lab. D-phenylalanine has more pain-relieving and opioid-increasing effects than the L- form because it inhibits the enzyme that breaks down opioids [R].
  • DL-phenylalanine is a mixture of the D- and L- kinds.

Health Benefits of Phenylalanine

1) May Help with Depression

Phenylalanine may increase euphoria and drive, and help with depression in some patients. However, we still don’t know exactly how it does this [R].

D-Phenylalanine supplements (75 – 200 mg/day) improved depression in 12 of 20 patients over the course of 20 days. At the end of 20 days, twelve of the patients were discharged without needing any further treatment [R].

Of the remaining eight patients, four showed mild to moderate antidepressant responses to the treatment, while the remaining 4 patients showed little to no improvement [R].

Many core symptoms of depression, such as depressed mood, agitation, and retardation, improved with phenylalanine. Anxiety and sleep disturbance were only somewhat improved. Phenylalanine had no effect on hypochondriasis (obsession over the idea that you have a serious but undiagnosable disease) and compulsiveness [R].

Some patients with depression have low urinary excretion of phenethylamine (a metabolized product of phenylalanine). It is hypothesized that with high phenethylamine levels, there is no improvement; so, the treatment could only benefit those with reduced phenethylamine [R].

Other studies showed similar improvement rates, and even if the treatment was not completely successful in some patients, the supplementation (by both DL and D-phenylalanine) produced no adverse effects [R].

2) May Help Treat Vitiligo

Phenylalanine can help treat vitiligo, which is a skin condition where the skin loses its color. Vitiligo is an autoimmune disease where the body’s own immune system attacks the cells that make the pigments in our skin(melanocytes) [R].

Topical and oral L-phenylalanine use, in addition to medication and UV therapy, greatly improved vitiligo in more than 75% of patients [R].

The treatment showed no side effects, highlighting the safety and usefulness of L-phenylalanine in treating vitiligo [R].

3) Indirectly Increases Dopamine Levels

Phenylalanine is the direct precursor of tyrosine in the human body [R].

Tyrosine can then be converted into dopamine. Dopamine plays an important part in many different physiological processes such as in pain perception and the reward system of the brain [RR].

The importance of proper dopamine levels can be seen in individuals with Phenylketonuria, a genetic disorder characterized by the inability to convert phenylalanine to tyrosine, which results in low dopamine levels. If left untreated, it can cause severe intellectual ability. Even in treated patients, deficits in executive functioning are correlated with reduced dopamine levels [R].

Therefore, increasing phenylalanine can indirectly increase catecholamine neurotransmitters, including dopamine, adrenaline, and noradrenaline levels [R].

In people with phenylalanine deficiencies, the decreased levels of phenylalanine lower the synthesis and release of dopamine [R].

In a study on participants that were deficient in phenylalanine, tyrosine supplementation decreased reaction time in response to a stimulus [R].

However, because tyrosine does not dissolve well in water, its direct supplementation is not efficient, which is why increasing phenylalanine concentrations could be a better alternative to produce more dopamine in the body [R].

4) May Enhance the Effectiveness of Acupuncture Anesthesia

D-Phenylalanine increases natural opioids in the body by inhibiting the enzyme carboxypeptidase, which degrades endogenous opioids in the body [R].

When 18 patients who underwent tooth extractions were given D-phenylalanine supplements before anesthesia, the effects of acupuncture anesthesia increased by 35% compared to the placebo group [R].

5) May Alleviate Alcohol Withdrawal Symptoms

When patients start alcohol-detoxification therapies, the stress due to withdrawal symptoms can reduce natural opioids (compounds that alleviate pain) and dopamine in the body. Phenylalanine can increase opioids and dopamine [R].

In a study of 20 patients (DB-RCT) suffering from alcohol withdrawal symptoms, those that received D-phenylalanine supplements showed a significant decrease in their psychiatric symptoms [R].

The treatment, which lasted 40 days, also showed that D-phenylalanine alleviated the stress common to all patients [R].

6) May Help Improve ADHD Symptoms in the Short Term

Low dopamine is believed to play a role in ADHD. Therefore, increasing dopamine levels by phenylalanine supplementation may help with ADHD symptoms.

In a study of 13 ADHD patients (DB-RCT), those that took DL-phenylalanine supplements showed improvements in symptoms such as anger, restlessness, and concentration [R].

The mood improvement seen in the treated group was likely due to increased dopamine synthesis [R, R, R].

However, three months after the study finished, the beneficial effects of the phenylalanine disappeared due to tolerance to the supplement [R].

Interestingly, increasing the dosage showed no effect once phenylalanine effectiveness started waning [R].

Because ADHD is a complex disease that varies from case to case, using phenylalanine in combination with other treatments may provide better outcomes [R].

7) Can be Used as a Marker for Parkinson’s Disease

Noninvasive methods for detecting Parkinson’s disease are not currently available [R].

Forty-nine percent of Parkinsons’ disease patients have blood tyrosine to phenylalanine ratios of less than the healthy level of 0.82. The lower blood tyrosine to phenylalanine ratio might be diagnostic of Parkinson’s [R].

Although Parkinson’s leads to loss of dopamine neurons and phenylalanine supplementation can regenerate dopamine, phenylalanine interferes with the absorption of L-dopa [R]. Therefore, phenylalanine should not be supplemented as a treatment for Parkinson’s disease.

Phenylalanine Supplement Reviews

Most people who take phenylalanine supplements find that it increases energy in a stimulating way, similar to the effect of coffee. The consensus seems to be that it helps them power through the day, even when their brains are feeling slow or tired. They also tend to eat less because the supplement reduces hunger and food cravings [R, R].

Those that take the supplement for depression say that it makes them feel more energetic, which helps them go about their everyday tasks [R, R].

Although the supplement provided more energy, most users don’t experience other stimulatory effects of dopamine (such as risk-taking) [R].

Phenylalanine Side Effects

1) May Increase Blood Pressure

In a case study (1 person), phenylalanine supplementation increased and decreased blood pressure to such extremes that he almost needed medical attention [R].

A side effect of phenylalanine supplementation is increased blood pressure. However, the response is usually not as severe as the one mentioned above [R].

2) May Increase Anxiety and Nightmares

Another user experienced increased anxiety due to unexpected laughing attacks. The user described the experience as a “nightmare,” so users should be cautious in taking the supplement and ask a doctor if its use is advisable [R].

3) Interferes with the Uptake of Parkinson’s Drug (L-dopa) into the Brain

Phenylalanine supplementation may actually interfere with the treatment of Parkinson’s disease [R].

A common occurrence in the disease is the “on-off” phenomenon where levodopa is not as well absorbed or transported at times [R].

During the “off” times of the disease, the patients are barely able to or cannot walk at all or accomplish their everyday tasks necessitating the need for a constantly “on” treatment [R].

Studies of nine patients showed that when phenylalanine-rich meals were taken, the levodopa concentrations in the blood decreased by 29% and the absorption was delayed by 34 minutes [R].

This happens due to the competing nature of levodopa and phenylalanine into the brain. Higher levels of phenylalanine can reduce the transport of levodopa into the brain reducing the effectiveness of the treatment [R].

Because of its strength, levodopa is usually given to patients with meals. A study indicates the need for more thorough examinations of the meals given to patients and their phenylalanine content when the drug is being administered [R].

4) Should Not be Taken by Those with Phenylketonuria (PKU)

Whether a phenylalanine-restricted diet is necessary for adult PKU patients is a hotly debated matter[R].

In a double-blind randomized controlled trial of nine adult PKU patients (DB-RCT), those that received the phenylalanine supplements showed attention and mood impairments, leading the authors to conclude that “A [phenylalanine]-restricted “diet for life” might be an advisable option for many” [R].

PKU patients should also avoid aspartame, a common derivative of phenylalanine that is used as a sugar substitute in many foods.

Limitations of Phenylalanine Supplementation

Findings on phenylalanine supplementation show contradictory results.

One of the biggest issues with phenylalanine supplementation is the tolerance that the body builds to the amino acid treatment [R].

The author warns that other phenylalanine studies may never have checked back on their patients once the study was concluded. Possibly, these studies have not investigated the tolerance and effectiveness of the treatment [R].

Genes and SNPs that Affect Phenylalanine Metabolism

Phenylalanine hydroxylase (PAH) gene is responsible for the conversion of phenylalanine into tyrosine. Mutations in this gene can lead to phenylketonuria (PKU) and decreased memory. In a study done on 599 adults, those with mutations in SNP rs2037639 generally had lower verbal memory [R].

The exact methodology into how the SNP affects phenylalanine metabolism is unknown. Some hypotheses laid forth were that the SNP may regulate the transcription of the PAH gene or that the SNP could be linked to another unknown functional SNP elsewhere so that a change in SNP rs2037639 could cause an alteration in phenylalanine levels [R].

Another human trial of 59 patients with phenylketonuria showed that mutations in the SNPs EX6-96 and R243Q of the PAH gene were the most common among those with PKU [R].

Foods High in Phenylalanine

Most foods that are high in protein will have high phenylalanine content. Some examples of some foods include dairy products such as milk and cheese and meat products such as chicken and beef [R].

Eggs, beans, and nuts are also high in phenylalanine content [R].

People with phenylketonuria are advised to stay away from foods with high phenylalanine content.

Phenylalanine Supplements

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